Current status of diversity by race, Hispanic ethnicity, and sex in diagnostic radiology.
To assess the diversity of the U.S. diagnostic radiology physician workforce by race, Hispanic ethnicity, and sex in the context of the available pipeline of medical students. Institutional review board evaluation and exemption were granted for the study, as primary data were obtained from publicly available registry sources, with no identifiable private or protected information. Publicly available American Medical Association, American Association of Medical Colleges, and U.S. census registries were used to assess differences for 2010 among diagnostic radiology practicing physicians, academic faculty, residents, subspecialty trainees, residency applicants, medical school graduates, and U.S. population by using binomial tests; with adjustment for multiple comparisons among different groups, differences with P < .001 were considered significant. Significant differences in diagnostic radiology resident representation were evaluated for academic years 2003-2004 to 2010-2011 and for 2010, compared among the 20 largest residency training programs. Females and traditionally underrepresented minorities in medicine (URM)-blacks, Hispanics, American Indians, Alaskan Natives, Native Hawaiians, and Pacific Islanders (AI/AN/NH/PI)-are underrepresented as practicing physicians (23.5% and 6.5%, respectively), faculty (26.1%, 5.9%), and diagnostic radiology residents (27.8%, 8.3%), compared with the U.S. population (50.8%, 30.0%) (all P < .001). Although they are increased in percentage as residents compared with practicing physicians, females and URMs remain underrepresented at the resident trainee level, compared with their proportions as medical school graduates (48.3%, 15.3%, respectively). During the past 8 years, there was no significant increase in female or URM resident (all P > .01) representation, suggesting no dramatic change in future representation as practicing physicians. Moreover, diagnostic radiology ranks 17th in female and 20th in URM representation among the 20 largest residency training specialties. Females and URM remain underrepresented in the diagnostic radiology physician workforce despite an available medical student pipeline. Given prevalent health care disparities and an increasingly diverse society, future research and training efforts should address increasing resident diversity with program directors and department chairs.


Automated Assessment of Existing Patient's Revised Cardiac Risk Index Using Algorithmic Software.
Previous work in the field of medical informatics has shown that rules-based algorithms can be created to identify patients with various medical conditions; however, these techniques have not been compared to actual clinician notes nor has the ability to predict complications been tested. We hypothesize that a rules-based algorithm can successfully identify patients with the diseases in the Revised Cardiac Risk Index (RCRI). Patients undergoing surgery at the University of California, Los Angeles Health System between April 1, 2013 and July 1, 2016 and who had at least 2 previous office visits were included. For each disease in the RCRI except renal failure-congestive heart failure, ischemic heart disease, cerebrovascular disease, and diabetes mellitus-diagnosis algorithms were created based on diagnostic and standard clinical treatment criteria. For each disease state, the prevalence of the disease as determined by the algorithm, International Classification of Disease (ICD) code, and anesthesiologist's preoperative note were determined. Additionally, 400 American Society of Anesthesiologists classes III and IV cases were randomly chosen for manual review by an anesthesiologist. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve were determined using the manual review as a gold standard. Last, the ability of the RCRI as calculated by each of the methods to predict in-hospital mortality was determined, and the time necessary to run the algorithms was calculated. A total of 64,151 patients met inclusion criteria for the study. In general, the incidence of definite or likely disease determined by the algorithms was higher than that detected by the anesthesiologist. Additionally, in all disease states, the prevalence of disease was always lowest for the ICD codes, followed by the preoperative note, followed by the algorithms. In the subset of patients for whom the records were manually reviewed, the algorithms were generally the most sensitive and the ICD codes the most specific. When computing the modified RCRI using each of the methods, the modified RCRI from the algorithms predicted in-hospital mortality with an area under the receiver operating characteristic curve of 0.70 (0.67-0.73), which compared to 0.70 (0.67-0.72) for ICD codes and 0.64 (0.61-0.67) for the preoperative note. On average, the algorithms took 12.64 ± 1.20 minutes to run on 1.4 million patients. Rules-based algorithms for disease in the RCRI can be created that perform with a similar discriminative ability as compared to physician notes and ICD codes but with significantly increased economies of scale.


Alzheimer's disease associated presenilin-1 holoprotein and its 18-20 kDa C-terminal fragment are death substrates for proteases of the caspase family.
Mutations in the presenilin (PS) genes are linked to early onset familial Alzheimer's disease (FAD). PS-1 proteins are proteolytically processed by an unknown protease leading to the formation of two stable fragments of approximately 30 and approximately 20 kDa [Thinakaran, G., et al. (1996) Neuron 17, 181-190]. In addition to the conventional fragments, alternative cleavage products were observed as well. Here we characterize an alternative proteolytic pathway of PS-1 which involves proteases of the caspase superfamily. Caspase mediated cleavage occurs between aspartate 345 and serine 346 C-terminal to the conventional cleavage determined previously [Podlisny, M., et al., (1997) Neurobiol. Dis. 3, 325-337]. Full-length PS-1 can serve as a substrate for caspase-like proteases, as demonstrated by the generation of the alternative C-terminal fragment in cells expressing PS-1 containing the Deltaexon 10 deletion which is known to accumulate as a full-length molecule [Thinakaran, G., et al. (1996)]. By inhibition of de novo protein synthesis in untransfected cells we demonstrate that the conventional C-terminal fragment of PS-1 is a substrate for caspase-like proteases as well. Therefore full-length and the conventional C-terminal fragment of PS-1 can serve as potential death substrates. Due to the fact that very little full-length PS-1 is expressed in vivo, the much more abundant C-terminal fragment and not the full-length precursor is the major in vivo substrate for the alternative cleavage of PS-1 by proteases of the caspase superfamily.


Scales for assessing self-efficacy of nurses and assistants for preventing falls.
This paper is a report of the development and testing of the Self-Efficacy for Preventing Falls Nurse and Assistant scales. Patient falls and fall-related injuries are traumatic ordeals for patients, family members and providers, and carry a toll for hospitals. Self-efficacy is an important factor in determining actions persons take and levels of performance they achieve. Performance of individual caregivers is linked to the overall performance of hospitals. Scales to assess nurses and certified nursing assistants' self-efficacy to prevent patients from falling would allow for targeting resources to increase SE, resulting in improved individual performance and ultimately decreased numbers of patient falls. Four phases of instrument development were carried out to (1) generate individual items from eight focus groups (four each nurse and assistant conducted in October 2007), (2) develop prototype scales, (3) determine content validity during a second series of four nurse and assistant focus groups (January 2008) and (4) conduct item analysis, paired t-tests, Student's t-tests and internal consistency reliability to refine and confirm the scales. Data were collected during February-December, 2008. The 11-item Self-Efficacy for Preventing Falls Nurse had an alpha of 0·89 with all items in the range criterion of 0·3-0·7 for item total correlation. The 8-item Self-Efficacy for Preventing Falls Assistant had an alpha of 0·74 and all items had item total correlations in the 0·3-0·7 range. The Self-Efficacy for Preventing Falls Nurse and Self-Efficacy for Preventing Falls Assistant scales demonstrated psychometric adequacy and are recommended to measure bedside staff's self-efficacy beliefs in preventing patient falls.


Relationship between mechanical properties and bond durability of short fiber-reinforced resin composite with universal adhesive.
The purpose of this study was to determine the relationship between mechanical properties and bond durability of short fiber-reinforced resin composite with universal adhesive. As controls, micro-hybrid and nano-hybrid resin composites were tested. The universal adhesives used were Scotchbond Universal, Adhese Universal, and G-Premio Bond. The fracture toughness and flexural properties of resin composites, and shear bond strength and shear fatigue strength of universal adhesive with resin composite using both total-etch and self-etch modes were determined. In the results, short fiber-reinforced resin composite showed significantly higher fracture toughness than did micro-hybrid and nano-hybrid resin composites. The flexural strength and modulus of short fiber-reinforced and nano-hybrid resin composites were significantly lower than were those of micro-hybrid resin composites. Regardless of etching mode, the shear bond strength of universal adhesives with short fiber-reinforced resin composite did not show any significant differences from micro-hybrid and nano-hybrid resin composites. The shear fatigue strength of universal adhesives with short fiber-reinforced resin composite and micro-hybrid resin composites were significantly higher than that of nano-hybrid resin composites. The results of this study suggest that the mechanical properties of short fiber-reinforced resin composite improve their bond durability with universal adhesive.


The association of anti-platelet factor 4/heparin antibodies with early and delayed thromboembolism after cardiac surgery.
Essentials We evaluated antibody status, thromboembolism and survival after cardiac surgery. Positive antibody tests are common - over 50% are seropositive at 30 days. Seropositivity did not increase thromboembolism or impair survival after cardiac surgery. Results show heparin induced thrombocytopenia antibody screening after surgery is not warranted. Background Heparin-induced thrombocytopenia (HIT) is a prothrombotic response to heparin therapy with platelet-activating, anti-platelet factor 4 (PF4)/heparin antibodies leading to thrombocytopenia associated with thromboembolism. Objective We tested the hypothesis that anti-PF4/heparin antibodies are associated with thromboembolism after cardiac surgery. Methods This multicenter, prospective cohort study collected laboratory and clinical data up to 30 days after surgery and longer-term clinical follow-up data. The primary outcome variable combined new arterial or venous thromboembolic complications (TECs) with all-cause death until 90 days after surgery. Laboratory analyses included platelet counts and anti-PF4/heparin antibody titers (GTI ELISA), with a confirmatory excess heparin step and serotonin release assay. Chi-square testing was used to test the relationship between our outcome and HIT antibody seropositivity. Results Initially, 1021 patients were enrolled between August 2006 and May 2009, and follow-up was completed in December 2014. Seropositivity defined by OD > 0.4 was common, being almost 20% preoperatively, > 30% by discharge, and > 60% by day 30. Death (1.7% within 30 days) or TECs (69 in total) were more likely if the partient was seronegative (OD < 0.4), but positivity defined by OD > 1.0 or including an excess heparin confirmatory step resulted in equal incidence of death or TECs, whether the patient was seronegative or seropositive. Incorporating the serotonin release assay for platelet-activating antibodies did not alter these findings. Conclusions Seropositivity for anti-PF4/heparin antibodies does not increase the risk of death or thromboembolism after cardiac surgery. Screening is not indicated, and seropositivity should only be interpreted in the context of clinical evidence for HIT. Duke IRB Protocol #00010736.


The gene expression profile of human umbilical vein endothelial cells stimulated by tumor necrosis factor alpha using DNA microarray analysis.
Stimulation of vascular endothelial cells by tumor necrosis factor alpha (TNFalpha) plays a critical role in the pathogenesis of inflammation and vascular diseases. Changes in the gene expression profile in cultured human umbilical vein endothelial cells (HUVEC) treated with TNFalpha was analyzed with high-density oligonucleotide arrays comprised of 35,000 genes. TNFalpha stimulation profoundly induced genes involved in signal transduction, leukocyte adhesion and chemoattraction. ICAM-1 mRNA (fold change 111.9) was most profoundly induced followed by TNFalpha receptor-associated factor 1 (TRAF1) (95.5), Bcl3 (71.8), IL8 (65.4), fractalkaine (62.4), E-selectin (48.0), lymphotoxin beta (41.3) and VCAM-1 (31.7). In addition to these previously known genes, 18 poorly characterized or novel genes known as ESTs profoundly induced by TNFalpha. Initial sequencing analysis identified three of these the genes for squalene epoxydase, chromodomain helicase DNA binding protein 4, and CLP respectively. Further analysis of these genes will provide important information about TNFalpha signaling and function in vascular endothelial cells.


Diabetes-induced oxidative stress is mediated by Ca2+-independent phospholipase A2 in neutrophils.
Neutrophils from people with poorly controlled diabetes present a primed phenotype and secrete excessive superoxide. Phospholipase A(2) (PLA(2))-derived arachidonic acid (AA) activates the assembly of NADPH oxidase to generate superoxide anion. There is a gap in the current literature regarding which PLA(2) isoform regulates NADPH oxidase activation. The aim of this study was to identify the PLA(2) isoform involved in the regulation of superoxide generation in neutrophils and investigate if PLA(2) mediates priming in response to pathologic hyperglycemia. Neutrophils were isolated from people with diabetes mellitus and healthy controls, and HL60 neutrophil-like cells were grown in hyperglycemic conditions. Incubating neutrophils with the Ca(2+)-independent PLA(2) (iPLA(2)) inhibitor bromoenol lactone (BEL) completely suppressed fMLP-induced generation of superoxide. The nonspecific actions of BEL on phosphatidic acid phosphohydrolase-1, p47(phox) phosphorylation, and apoptosis were ruled out by specific assays. Small interfering RNA knockdown of iPLA(2) inhibited superoxide generation by neutrophils. Neutrophils from people with poorly controlled diabetes and in vitro incubation of neutrophils with high glucose and the receptor for advanced glycation end products ligand S100B greatly enhanced superoxide generation compared with controls, and this was significantly inhibited by BEL. A modified iPLA(2) assay, Western blotting, and PCR confirmed that there was increased iPLA(2) activity and expression in neutrophils from people with diabetes. AA (10 microM) partly rescued the inhibition of superoxide generation mediated by BEL, confirming that NADPH oxidase activity is, in part, regulated by AA. This study provides evidence for the role of iPLA(2) in enhanced superoxide generation in neutrophils from people with diabetes mellitus and presents an alternate pathway independent of protein kinase C and phosphatidic acid phosphohydrolase-1 hydrolase signaling.


The Arabidopsis FILAMENTOUS FLOWER gene is required for flower formation.
A screen for mutations affecting flower formation was carried out and several filamentous flower (fil) alleles were identified. In fil mutants, floral primordia occasionally give rise to pedicels lacking flowers at their ends. This defect is dramatically enhanced in fil rev double mutants, in which every floral primordium produces a flowerless pedicel. These data suggest that the FIL and REV genes are required for an early step of flower formation, possibly for the establishment of a flower-forming domain within the floral primordium. The FIL gene is also required for establishment of floral meristem identity and for flower development. During flower development, the FIL gene is required for floral organ formation in terms of the correct numbers and positions; correct spatial activity of the AGAMOUS, APETALA3, PISTILLATA and SUPERMAN genes; and floral organ development.


Effect of rate of body weight gain in steers during the stocker phase. I. Growth, partitioning of fat among depots, and carcass characteristics of growing-finishing beef cattle.
Two experiments were conducted to examine the effect of growth rate to similar age or BW on fat deposition in stocker cattle grazing dormant native range (DNR) or winter wheat pasture (WP). In each experiment, fall-weaned Angus steers were randomly allotted to 1 of 4 stocker production programs: 1) control, 1.02 kg/d of a 40% CP cottonseed meal-based supplement during grazing of DNR (CON); 2) corn/soybean meal-based supplement fed at 1% of BW during grazing of DNR (CORN); 3) grazing WP at a high stocking rate to achieve a low rate of BW gain (LGWP); and 4) grazing WP at a low stocking rate to achieve a high rate of BW gain (HGWP). In Exp. 1, a subset of steers (3 steers per treatment) was harvested after winter grazing (138 d) at similar age. The remaining WP steers were transitioned into the finishing phase, whereas DNR steers were allowed to graze the same native range pastures for another 115 d without supplementation before entering the feedyard. In Exp. 2, steers grazed their respective pastures until each treatment reached an estimated HCW of 200 kg (262, 180, 142, and 74 d, respectively, for the CON, CORN, LGWP, and HGWP treatments), at which time a subset of steers (4 steers per treatment) were selected for intermediate harvest before finishing. In both experiments, the remaining steers were fed a finishing diet to a common 12th-rib fat thickness of 1.27 cm. In Exp. 1, winter grazing ADG was 0.19, 0.52, 0.68, and 1.37 ± 0.03 kg/d; and in Exp. 2, winter/summer grazing ADG was 0.46, 0.61, 0.83, and 1.29 ± 0.02 kg/d, respectively for CON, CORN, LGWP, and HGWP treatments. At intermediate harvest in Exp. 1, HGWP steers had greater (P < 0.01) 12th-rib fat thickness and marbling scores, compared with the other treatments. However, in Exp. 2, LGWP steers had greater (P < 0.01) marbling scores compared with HGWP steers, which were greater than DNR steers. At final harvest in Exp. 1, LGWP steers had greater (P < 0.01) 12th-rib fat thickness and smaller LM area, compared with the other treatments; however, there were no differences (P = 0.99) in final marbling scores. In Exp. 2, CON steers had lower (P < 0.05) 12th-rib fat thickness and tended (P = 0.10) to have greater marbling scores, compared with the other treatments. These data suggest that changes in the partitioning of fat among depots during the stocker phase may not be reflected after finishing when steers are fed to a common 12th-rib fat thickness.


Handling Sign Language Data: The Impact of Modality.
Natural languages come in two different modalities. The impact of modality on the grammatical structure and linguistic theory has been discussed at great length in the last 20 years. By contrast, the impact of modality on linguistic data elicitation and collection, corpus studies, and experimental (psycholinguistic) studies is still underinvestigated. In this article, we address specific challenges that arise in judgment data elicitation and experimental studies of sign languages. These challenges are related to the socio-linguistic status of the Deaf community and the larger variability across signers within the same community, to the social status of sign languages, to properties of the visual-gestural modality and its interface with gesture, to methodological aspects of handling sign language data, and to specific linguistic features of sign languages. While some of these challenges also pertain to (some varieties of) spoken languages, other challenges are more modality-specific. The special combination of the challenges discussed in this article seems to be a specific facet empirical research on sign languages is faced with. In addition, we discuss the complementarity of theoretical approaches and experimental studies and show how the interaction of both approaches contributes to a better understanding of sign languages in particular and linguistic structures in general.


Volcanogenic pollution and testicular damage in wild mice.
Many evidences have surfaced the adverse effects of environmental pollutants on male reproduction. Volcanogenic pollution is understudied, although it is a well-known source of hazardous contaminants. This study aims to assess the effects of chronic exposure to volcanogenic pollution on wild mice testes by studying: (i) diameter of seminiferous tubules; (ii) relative volumetric density of different spermatogenic cells and interstitial space; (iii) damage in the seminiferous tubules and (iv) apoptotic level in the germinal epithelium. The mice from the polluted site showed higher levels of the selected heavy metals than those from the reference site. The mean diameter of seminiferous tubules and the relative volume occupied by spermatozoa and lumen in exposed mice were significantly lower than in the unexposed group. Contrarily, exposed mice showed a significantly higher relative volume occupied by interstitium, as well as, a higher degree of damage and a significantly higher number of apoptotic cells in the germinal epithelium. Results show that secondary manifestations of volcanic activity can pose a serious risk of testicular injury and therefore for male reproduction.


Secondary ischaemia in rabbit skin flaps: the roles played by thromboxane and free radicals.
1. Biochemical mechanisms of ischaemia were investigated in rabbit skin flaps subjected to 2 h of primary ischaemia then, 24 h later, to 4 h of secondary ischaemia. During secondary ischaemia, flaps underwent either total ischaemia (arterial and venous blood supply occluded) or partial ischaemia (vein only occluded). Some of these flaps were treated at the time of reperfusion with the free-radical scavenger superoxide dismutase (EC 18.104.22.168) and/or the thromboxane synthetase inhibitor UK-38,485. 2. After 30 min of reperfusion, superoxide dismutase treatment significantly reduced blood thromboxane levels, elevated during ischaemia. Superoxide dismutase also reduced tissue levels of malonyldialdehyde and xanthine oxidase, indicators of free-radical damage, and restored the depleted tissue levels of superoxide dismutase. 3. UK-38,485 treatment failed to significantly alter any of these tissue free-radical parameters, although this agent significantly reduced blood thromboxane levels. 4. Combined superoxide dismutase plus UK-38,485 treatment was not significantly better than either treatment alone with respect to any parameter. 5. Partial ischaemia led to consistently higher levels of tissue free radicals and blood thromboxane than did total ischaemia. Thus partial ischaemia appears to result in greater free-radical damage than total ischaemia. 6. These results are consistent with the hypothesis that thromboxane acts as a mediator for free-radical damage in the ischaemic changes within the flap.


Developing Interprofessional Education at One U.S. Dental School: Establishing a Baseline and Moving Forward.
Dental schools across the U.S. are in the process of incorporating interprofessional education (IPE) into their curricula. At Louisiana State University Health Sciences Center-New Orleans (LSUHSC), the process of educating competent students fully prepared to maximize patient outcomes through interprofessional care is under way. The aim of this study was to establish baseline data on three years of LSU dental students' perceptions of IPE prior to and as a new two-year IPE curriculum was being introduced. A survey was conducted of dental students in all four years from 2015 to 2017 using the Student Perceptions of Interprofessional Clinical Education-Revised instrument, version 2 (SPICE-R2). In 2015, 120 students participated in the survey for a response rate of 46%, followed by 160 students in 2016 (62%) and 170 in 2017 (67%). The results showed that the first-year students in 2017 had a higher total SPICE-R2 mean score than the first-year students in 2015 and 2016; the difference was statistically significant. Even though the 2017 first-year students had only received an orientation to the curriculum at the time they completed the survey, this change in attitude suggests the new focus on IPE was already having an effect on students. There were no statistically significant differences between mean scores for the three cohorts of second-, third-, and fourth-year students, none of whom had experienced the new IPE curriculum. Data from this study will serve as a baseline from which to evaluate the impact of the new IPE curriculum that is now required of all first- and second-year dental students. Through continued IPE exposure in the curriculum and ongoing faculty development, further improvements in students' attitudes toward IPE can be anticipated.


Stride-to-stride variability while backward counting among healthy young adults.
Little information exists about the involvement of attention in the control of gait rhythmicity. Variability of both stride time and stride length is closely related to the control of the rhythmic stepping mechanism. We sought 1) to determine whether backward counting while walking could provoke significant gait changes in mean values and coefficients of variation of stride velocity, stride time and stride length among healthy young adults; and 2) to establish whether change in stride-to-stride variability could be related to dual-task related stride velocity change, attention, or both. Mean values and coefficients of variation of stride velocity, stride time and stride length were recorded using the Physilog-system, at a self-selected walking speed in 49 healthy young adults (mean age 24.1 +/- 2.8 years, women 49%) while walking alone and walking with simultaneous backward counting. Performance on backward counting was evaluated by recording the number of figures counted while sitting alone and while walking. Compared with walking alone, a significant dual-task-related decrease was found for the mean values of stride velocity (p < 0.001), along with a small but significant increase for the mean values and coefficients of variation of stride time (p < 0.001 and p = 0.015, respectively). Stride length parameters did not change significantly between both walking conditions. Dual-task-related increase of coefficient of variation of stride time was explained by changing stride velocity and variability between subjects but not by backward counting. The number of figures counted while walking decreased significantly compared to backward counting alone. Further, the dual-task related decrease of the number of enumerated figures was significantly higher than the dual-task related decrease of stride velocity (p = 0.013). The observed performance-changes in gait and backward counting while dual tasking confirm that certain aspects of walking are attention-demanding in young adults. In the tested group of 49 young volunteers, dual tasking caused a small decrease in stride velocity and a slight increase in the stride-to-stride variability of stride time, while stride velocity variability was not affected by the attention-demanding task. The increase in stride time variability was apparently the result of a change in gait speed, but not a result of dual tasking. This suggests that young adults require minimal attention for the control of the rhythmic stepping mechanism while walking.


Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptor-beta expression or serum hormonal profiles in men at high risk of prostate cancer.
The purpose of this study was to determine the effects of soy protein isolate consumption on circulating hormone profiles and hormone receptor expression patterns in men at high risk for developing advanced prostate cancer. Fifty-eight men were randomly assigned to consume 1 of 3 protein isolates containing 40 g/d protein: 1) soy protein isolate (SPI+) (107 mg/d isoflavones); 2) alcohol-washed soy protein isolate (SPI-) (<6 mg/d isoflavones); or 3) milk protein isolate (0 mg/d isoflavones). For 6 mo, the men consumed the protein isolates in divided doses twice daily as a partial meal replacement. Serum samples collected at 0, 3, and 6 mo were analyzed for circulating estradiol, estrone, sex hormone-binding globulin, androstenedione, androstanediol glucuronide, dehydroepiandrosterone sulfate, dihydrotestosterone, testosterone, and free testosterone concentrations by RIA. Prostate biopsy samples obtained pre- and postintervention were analyzed for androgen receptor (AR) and estrogen receptor-beta expression by immunohistochemistry. At 6 mo, consumption of SPI+ significantly suppressed AR expression but did not alter estrogen receptor-beta expression or circulating hormones. Consumption of SPI- significantly increased estradiol and androstenedione concentrations, and tended to suppress AR expression (P = 0.09). Although the effects of SPI- consumption on estradiol and androstenedione are difficult to interpret and the clinical relevance is uncertain, these data show that AR expression in the prostate is suppressed by soy protein isolate consumption, which may be beneficial in preventing prostate cancer.


Phase II trials of flavone acetic acid in advanced malignant melanoma and colorectal carcinoma.
Flavone acetic acid (FAA), 8.6 gm-2 has been administered by 6h intravenous infusion to 19 patients with advanced colorectal carcinoma and 15 patients with advanced malignant melanoma. The drug associated toxicity was generally mild and as predicted from the phase I study. No responses were seen in either disease.


Spatial non-homogeneity of the antagonistic surround in motion perception.
At high contrast, duration thresholds for motion direction discrimination deteriorate with increasing stimulus size. This counterintuitive result has been explained by the center-surround antagonism present in the neurons of visual area MT. Conversely, at very low contrast, direction discrimination improves with increasing size, a result that has been explained by spatial summation. In this investigation, we study the effects of stimulus shape and contrast on center-surround antagonism. Using adaptive Bayesian staircases, we measured duration thresholds of 5 subjects for vertically oriented Gabor patches of 1 cycle/deg with two types of oval Gaussian windows, one vertically elongated (Sx = 0.35, Sy = 2.5 deg) and other horizontally elongated (Sx = 2.5, Sy = 0.35 deg) moving rightward or leftward at a speed of 2 deg/s. We found that at high contrast (92%) duration thresholds were lower for vertically than horizontally elongated windows. However, at low contrast (2.8%), we found that duration thresholds were lower for horizontally than vertically elongated windows. These asymmetric results mirror the spatial non-homogeneity of the antagonistic surround found in MT neurons and suggest that the underlying center-surround antagonism is stronger along the direction of motion.


Dissipation and fluctuations in nanoelectromechanical systems based on carbon nanotubes.
The tribological characteristics of nanotube-based nanoelectromechanical systems (NEMS) exemplified by a gigahertz oscillator are studied. Various factors that influence the tribological properties of nanotube-based NEMS are quantitatively analyzed with the use of molecular dynamics calculations of the quality factor (Q-factor) of the gigahertz oscillator. We demonstrate that commensurability of the nanotube walls can increase the dissipation rate, while the structure of the wall ends and the nanotube length do not influence the Q-factor. It is shown that the dissipation rate depends on the interwall distance and the way of fixation of the outer wall, and is significant in the case of a poor fixation for nanotubes with a large interwall distance. Defects are found to strongly decrease the Q-factor due to the excitation of low-frequency vibrational modes. No universal correlation between the static friction forces and the energy dissipation rate is established. We propose an explanation of the obtained results on the basis of the classical theory of vibrational-translational relaxation. Significant thermodynamics fluctuations are revealed in the gigahertz oscillator by molecular dynamics simulations and they are analyzed in the framework of the fluctuation-dissipation theorem. The possibility of designing NEMS with a desirable Q-factor and their applications are discussed on the basis of the above results.


Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic.
The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission. We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.


Indoleamine 2,3-dioxygenase-1 is protective in atherosclerosis and its metabolites provide new opportunities for drug development.
Atherosclerosis is the major cause of cardiovascular disease (CVD), the leading cause of death worldwide. Despite much focus on lipid abnormalities in atherosclerosis, it is clear that the immune system also has important pro- and antiatherogenic functions. The enzyme indoleamine-2,3-dioxygenase (IDO) catalyses degradation of the essential amino acid tryptophan into immunomodulatory metabolites. How IDO deficiency affects immune responses during atherogenesis is unknown and we explored potential mechanisms in models of murine and human atherosclerosis. IDO deficiency in hypercholesterolemic ApoE(-/-) mice caused a significant increase in lesion size and surrogate markers of plaque vulnerability. No significant changes in cholesterol levels were observed but decreases in IL-10 production were found in the peripheral blood, spleen and lymph node B cells of IDO-deficient compared with IDO-competent ApoE(-/-) mice. 3,4,-Dimethoxycinnamoyl anthranilic acid (3,4-DAA), an orally active synthetic derivative of the tryptophan metabolite anthranilic acid, but not l-kynurenine, enhanced production of IL-10 in cultured splenic B cells. Finally, 3,4-DAA treatment reduced lesion formation and inflammation after collar-induced arterial injury in ApoE(-/-) mice, and reduced cytokine and chemokine production in ex vivo human atheroma cell cultures. Our data demonstrate that endogenous production of tryptophan metabolites via IDO is an essential feedback loop that controls atherogenesis and athero-inflammation. We show that the IDO pathway induces production of IL-10 in B cells in vivo and in vitro, suggesting that IDO may induce immunoregulatory functions of B cells in atherosclerosis. The favorable effects of anthranilic acid derivatives in atherosclerosis indicate a novel approach toward therapy of CVD.


Radioembolization with use of yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis.
Intraarterial delivery of yttrium-90 ((90)Y)-bound microspheres (ie, radioembolization) is a promising treatment for hepatocellular carcinoma (HCC). An early concern was the "embolic" nature of the microspheres, and their potential to reduce hepatic arterial blood flow in patients with compromised portal blood flow secondary to portal vein thrombosis/occlusion (PVT). In this situation, the risk of liver failure could be enhanced, particularly in patients with cirrhosis who have increased hepatic arterial blood flow. This retrospective analysis was undertaken to assess the safety and clinical benefits of radioembolization with (90)Y resin microspheres in HCC with branch or main PVT. A total of 25 patients presenting with unresectable HCC and compromised portal flow received segmental, lobar, or whole-liver infusion of (90)Y resin microspheres. For the analysis of tumor response, changes in target lesions, appearance of new lesions, and changes in portal vein thrombus were studied. Controlled disease was defined by absence of progression in all these components. Globally, controlled disease was achieved in 66.7% of patients at 2 months and 50% of patients at 6 months. No significant changes were observed in liver-related toxicities according to Common Toxicity Criteria (version 3.0) at 1 and 2 months after treatment. Median survival time was 10 months (95% CI, 6.6-13.3 months). Radioembolization of unresectable HCC and branch or main PVT with (90)Y resin microspheres was associated with minimal toxicity and a favorable median survival time. Further prospective studies are warranted to validate the findings in this clinically challenging patient population.


CFA-4 - a fluorinated metal-organic framework with exchangeable interchannel cations.
The syntheses and crystal structures of the fluorinated linker 1,4-bis(3,5-bis(trifluoromethyl)-1H-pyrazole-4-yl)benzene (H2-tfpb; 1) and the novel metal-organic framework family M[CFA-4] (Coordination Framework Augsburg University-4), M[Cu5(tfpb)3] (M = Cu(i), K, Cs, Ca(0.5)), are described. The ligand 1 is fully characterized by single crystal X-ray diffraction, photoluminescence-, NMR-, IR spectroscopy, and mass spectrometry. The copper(i)-containing MOF crystallizes in the hexagonal crystal system within the chiral space group P6322 (no. 182) and the unit cell parameters are as follows: a = 23.630(5) Å, c = 41.390(5) Å, V = 20 015(6) Å3. M[CFA-4] features a porous 3-D structure constructed from pentanuclear copper(i) secondary building units {Cu(pz)6}- (pz = pyrazolate). Cu(I)[CFA-4] is fully characterized by synchrotron single crystal X-ray diffraction, thermogravimetric analysis, variable temperature powder X-ray diffraction, IR spectroscopy, photoluminescence and gas sorption measurements. Moreover, thermal stability and gas sorption properties of K[CFA-4] and Cu(I)[CFA-4] are compared.


Assessing the effect of regularization on the molecular properties predicted by SCAN and self-interaction corrected SCAN meta-GGA.
Recent regularization of the SCAN meta-GGA functional (rSCAN) has simplified the numerical complexities of the SCAN functional, alleviating SCAN's stringent demand on the numerical integration grids to some extent. The regularization of rSCAN, however, results in the breaking of some constraints such as the uniform electron gas limit, the slowly varying density limit, and coordinate scaling of the iso-orbital indicator. Here, we assess the effects of regularization on the electronic, structural, vibrational, and magnetic properties of molecules by comparing the SCAN and rSCAN predictions. The properties studied include atomic energies, atomization energies, ionization potentials, electron affinities, barrier heights, infrared intensities, dissociation and reaction energies, spin moments of molecular magnets, and isomer ordering of water clusters. Our results show that rSCAN requires less dense numerical grids and gives very similar results to those of SCAN for all properties examined with the exception of atomization energies, which are worsened in rSCAN. We also examine the performance of self-interaction-corrected (SIC) rSCAN with respect to SIC-SCAN using the Perdew-Zunger (PZ) SIC method. The PZSIC method uses orbital densities to compute one-electron self-interaction errors and places an even more stringent demand on numerical grids. Our results show that SIC-rSCAN gives marginally better performance than SIC-SCAN for almost all properties studied in this work with numerical grids that are on average half or less as dense as that needed for SIC-SCAN.


The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates.
Activation-induced cytidine deaminase (AID) initiates immunoglobulin (Ig) heavy-chain (IgH) class switch recombination (CSR) and Ig variable region somatic hypermutation (SHM) in B lymphocytes by deaminating cytidines on template and nontemplate strands of transcribed DNA substrates. However, the mechanism of AID access to the template DNA strand, particularly when hybridized to a nascent RNA transcript, has been an enigma. We now implicate the RNA exosome, a cellular RNA-processing/degradation complex, in targeting AID to both DNA strands. In B lineage cells activated for CSR, the RNA exosome associates with AID, accumulates on IgH switch regions in an AID-dependent fashion, and is required for optimal CSR. Moreover, both the cellular RNA exosome complex and a recombinant RNA exosome core complex impart robust AID- and transcription-dependent DNA deamination of both strands of transcribed SHM substrates in vitro. Our findings reveal a role for noncoding RNA surveillance machinery in generating antibody diversity.


Crown and root lengths of incisors, canines, and premolars measured by cone-beam computed tomography in patients with malocclusions.
The purposes of this study were to determine the accuracy of crown and root length measurements of premolars using cone-beam computed tomography (CBCT) and to generate reference CBCT-based data on incisor, canine, and premolar lengths in patients with malocclusions. Imaging was performed using a CBCT scanner with a 0.292-mm voxel size and 12-bit grayscale. The CBCT-based length measurements were compared with direct measurements of 94 subsequently extracted premolars without metal restorations using the paired t-test. Furthermore, the crown and root lengths of incisors, canines, and premolars in 62 Korean patients with malocclusions were measured using CBCT, and Pearson's correlation coefficients were calculated to examine the relationship between the crown and root length measurements of each tooth type. The differences between the CBCT-based and direct measurements of the extracted premolars were not significant, with 95% limits of agreement of -0.90 to 0.90 mm for crown length and -1.23 to 1.18 mm for root length. Weak positive correlations between the crown and root length measurements were observed for the mandibular canine and premolars. The CBCT-based measurements showed a wider range of limits of agreements for root length than for crown length. The CBCT-based data can be used as a reference for evaluating root length and resorption of teeth without metal restorations in patients with malocclusions.


Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population.
Our aim was to test if plasma copeptin, a stable surrogate marker of arginine vasopressin, predicts decline of glomerular filtration rate (GFR) and risk of chronic kidney disease (CKD). We measured copeptin and renal function at the Malmö Diet and Cancer Cardiovascular Cohort baseline exam and reassessed renal function after a follow-up time of 16.6 ± 1.5 years (n = 3,186). Furthermore, we defined CKD based on an estimated GFR (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) <60 (CKD_60MDRD), <45 (CKD_45MDRD) and <30 (CKD_30MDRD) ml/min/1.73 m2. After multivariate adjustment (gender, age, baseline eGFR, smoking status, systolic blood pressure, antihypertensive treatment and follow-up time), copeptin (beta-coefficient per 1 SD increment of copeptin) was independently associated with significantly greater annual decline of eGFR (ml/min/1.73 m2) according to the MDRD formula (OR 0.057, 95% CI 0.022-0.093; p = 0.001) as well as according to the CKD Epidemiology Collaboration (CKD-EPI) formula (OR 0.050, 95% CI 0.022-0.077; p < 0.001). Each SD increment of copeptin independently predicted incident CKD_60MDRD (OR 1.19, 95% CI 1.04-1.36; p = 0.010), CKD_45MDRD (OR 1.33, 95% CI 1.04-1.71; p = 0.026) and CKD_30MDRD (OR 3.69, 95% CI 1.41-9.66; p = 0.008). The relationship between copeptin and CKD defined by CKD-EPI gave similar results. Our data suggest that increased levels of copeptin independently predict decline in eGFR and greater risk of new-onset CKD.


Elevated hippocampal resting-state connectivity underlies deficient neurocognitive function in aging.
The brain is not idle during rest. Functional MRI (fMRI) studies have identified several resting-state networks, including the default mode network (DMN), which contains a set of cortical regions that interact with a hippocampus (HC) subsystem. Age-related alterations in the functional architecture of the DMN and HC may influence memory functions and possibly constitute a sensitive biomarker of forthcoming memory deficits. However, the exact form of DMN-HC alterations in aging and concomitant memory deficits is largely unknown. Here, using both task and resting data from 339 participants (25-80 y old), we have demonstrated age-related decrements in resting-state functional connectivity across most parts of the DMN, except for the HC network for which age-related elevation of connectivity between left and right HC was found along with attenuated HC-cortical connectivity. Elevated HC connectivity at rest, which was partly accounted for by age-related decline in white matter integrity of the fornix, was associated with lower cross-sectional episodic memory performance and declining longitudinal memory performance over 20 y. Additionally, elevated HC connectivity at rest was associated with reduced HC neural recruitment and HC-cortical connectivity during active memory encoding, which suggests that strong HC connectivity restricts the degree to which the HC interacts with other brain regions during active memory processing revealed by task fMRI. Collectively, our findings suggest a model in which age-related disruption in cortico-hippocampal functional connectivity leads to a more functionally isolated HC at rest, which translates into aberrant hippocampal decoupling and deficits during mnemonic processing.


Estimating the proportion of true null hypotheses for multiple comparisons.
Whole genome microarray investigations (e.g. differential expression, differential methylation, ChIP-Chip) provide opportunities to test millions of features in a genome. Traditional multiple comparison procedures such as familywise error rate (FWER) controlling procedures are too conservative. Although false discovery rate (FDR) procedures have been suggested as having greater power, the control itself is not exact and depends on the proportion of true null hypotheses. Because this proportion is unknown, it has to be accurately (small bias, small variance) estimated, preferably using a simple calculation that can be made accessible to the general scientific community. We propose an easy-to-implement method and make the R code available, for estimating the proportion of true null hypotheses. This estimate has relatively small bias and small variance as demonstrated by (simulated and real data) comparing it with four existing procedures. Although presented here in the context of microarrays, this estimate is applicable for many multiple comparison situations.


Molecular genetics research in sub-Saharan Africa: how can the international community help?
Opportunities provided by rapidly increasing access to educational resources, clinical and epidemiological data, DNA collections, cheaper technology and financial investment, suggest that researchers in sub-Saharan Africa outside South Africa (SSAOSA) could now join the genomics revolution on equal terms with those in the West. Current evidence, however, suggests that, in some cases, various factors may be compromising this development. One interpretation is that urgent practical problems, which may compromise motivation, aspiration and ambition, are blocking opportunity. Those wishing to help should support the SSAOSA scientists both at the level of extending collaboration networks and in stimulating academic leadership at national and institutional levels to ensure adequate resources are allocated. Members of organisations representing the international community of human geneticists, such as HUGO, have a significant responsibility in supporting such activities.


First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic β-cell mass.
Whole-organism chemical screening can circumvent bottlenecks that impede drug discovery. However, in vivo screens have not attained throughput capacities possible with in vitro assays. We therefore developed a method enabling in vivo high-throughput screening (HTS) in zebrafish, termed automated reporter quantification in vivo (ARQiv). In this study, ARQiv was combined with robotics to fully actualize whole-organism HTS (ARQiv-HTS). In a primary screen, this platform quantified cell-specific fluorescent reporters in >500,000 transgenic zebrafish larvae to identify FDA-approved (Federal Drug Administration) drugs that increased the number of insulin-producing β cells in the pancreas. 24 drugs were confirmed as inducers of endocrine differentiation and/or stimulators of β-cell proliferation. Further, we discovered novel roles for NF-κB signaling in regulating endocrine differentiation and for serotonergic signaling in selectively stimulating β-cell proliferation. These studies demonstrate the power of ARQiv-HTS for drug discovery and provide unique insights into signaling pathways controlling β-cell mass, potential therapeutic targets for treating diabetes.


Off-axis electron holography of unbiased and reverse-biased focused ion beam milled Si p-n junctions.
Off-axis electron holography is used to measure electrostatic potential profiles across a silicon p-n junction, which has been prepared for examination in the transmission electron microscope (TEM) in two different specimen geometries using focused ion beam (FIB) milling. Results are obtained both from a conventional unbiased FIB-milled sample and using a novel sample geometry that allows a reverse bias to be applied to an FIB-milled sample in situ in the TEM. Computer simulations are fitted to the results to assess the effect of TEM specimen preparation on the charge density and the electrostatic potential in the thin sample.


Chronic toxicity of five metals to the polar marine microalga Cryothecomonas armigera - Application of a new bioassay.
The paucity of ecotoxicological data for Antarctic organisms is impeding the development of region-specific water quality guidelines. To address this limitation, toxicity testing protocols need to be developed to account for the unique physiology of polar organisms, in particular their slow growth rates. In this study, a toxicity test protocol was developed to investigate the toxicities of five metals to the polar marine microalga Cryothecomonas armigera. The concentrations which reduced population growth rate by 10% (EC10) after 24-d for Cu, Pb, Zn, Cd and Ni were 21.6, 152, 366, 454, and 1220 μg.L-1, respectively. At the concentrations used in tests, only Cu and Ni were sufficiently toxic to enable the derivation of EC50 values of 63.1 and 1570 μg.L-1 respectively. All metals affected C. armigera's cellular physiology including cellular chlorophyll a fluorescence, cell complexity and size, and lipid concentrations. However, no changes to cellular membrane permeability were observed. The reduction in cellular lipid concentrations was a more sensitive indicator of toxicity for Cd, Ni, and Pb than growth rate inhibition, with EC10 values of 89, 894, and 11 μg.L-1, respectively, highlighting its potential as a sensitive measure of metal toxicity.


A coupled chemical-genetic and bioinformatic approach to Polo-like kinase pathway exploration.
Protein phosphorylation is a ubiquitous mechanism for cellular signal propagation, and signaling network complexity presents a challenge to protein kinase substrate identification. Few targets of Polo-like kinases are known, despite their significant role in coordinating cell-cycle progression. Here, we combine chemical-genetic, bioinformatic, and proteomic tools for Polo-like kinase substrate identification. Specific pharmacological inhibition of budding yeast Polo-like kinase, Cdc5, resulted in a misaligned preanaphase spindle and subsequently delayed anaphase nuclear migration, revealing a Cdc5 function. A cellular screen for Cdc5 substrates identified Spc72, a spindle pole body (SPB) component and microtubule anchor required for nuclear positioning. Spc72 bound to the Cdc5 PBD in a mitosis-specific manner, was phosphorylated by Cdc5 in vitro, and demonstrated a loss of mitotic phosphorylation in vivo upon Cdc5 inhibition. Finally, an examination of Cdc5 binding by SPB-localized proteins expanded our knowledge of Cdc5 function at the SPB.


Consensus Guidelines on Genetic` Testing for Hereditary Breast Cancer from the American Society of Breast Surgeons.
The purpose of this consensus guideline is to outline recommendations for genetic testing that medical professionals can use to assess hereditary risk for breast cancer. Literature review included large datasets, basic and clinical science publications, and recent updated national guidelines. Genetic testing to assess hereditary risk of cancer is a complex, broad, and dynamic area of medical research. The dominant focus of this guideline is limited in scope to breast cancer. There is a lack of consensus among experts regarding which genes among many should be tested in different clinical scenarios. There is also variation in the degree of consensus regarding the understanding of risk and appropriate clinical management of mutations in many genes. Genetic testing should be made available to all patients with a personal history of breast cancer. Recent data are reviewed that support genetic testing being offered to each patient with breast cancer (newly diagnosed or with a personal history). If genetic testing is performed, such testing should include BRCA1/BRCA2 and PALB2, with other genes as appropriate for the clinical scenario and family history. For patients with newly diagnosed breast cancer, identification of a mutation may impact local treatment recommendations. Patients who had genetic testing previously may benefit from updated testing. Genetic testing should be made available to patients without a history of breast cancer who meet National Comprehensive Cancer Network guidelines. Finally, variants of uncertain significance are not clinically actionable and these patients should be managed based on their individual risk factors.


Effect of a 24-week physical training programme (in water and on land) on pain, functional capacity, body composition and quality of life in women with fibromyalgia.
To analyse the effect of a 24-week physical training programme in water and on land on women with fibromyalgia. A controlled study was conducted from December 2009 to May 2010. Seventy-two women with fibromyalgia (age: 51.79±7.87 years) were assigned to an exercise group (3 sessions/week, 2 sessions in water, 1 session on land) (n=42) and to a control group (n=30). The variables analysed were: number of tender points, visual analogue scale (VAS) of pain, algometer score, functional capacity (leg strength, hand-grip dynamometry, flexibility, agility, balance, aerobic endurance, heart response), body composition (body mass index, fat mass index, skeletal muscle mass index and percentage of body fat) and psychological variables (Fibromyalgia Impact Questionnaire [FIQ] and Short Form Health Survey 36 [SF-36]). The exercise group improved in the algometer score (p<0.001), positive tender points (p=0.005), VAS (p<0.001) and FIQ (p<0.001). Improvements were also detected in functional capacity (leg strength, p=0.001; hand-grip dynamometry, p=0.001; flexibility, p<0.001; balance, p=0.006; 6-minute walk test, p<0.001; mean heart rate, p=0.031; maximum heart rate, p<0.001 and VO2 max, p<0.001). There was a decrease in the percentage of body fat (p=0.040). There was also an improvement in the subscales of the SF-36; vitality (p=0.004), mental health (p=0.001) social role functioning (p=0.020) and general health functioning (p=0.002). The findings of this study show that a 24-week physical training programme (3 sessions/week, of which 2 sessions are in water and 1 session is on land) reduces pain and disease impact and improves functional capacity in women with fibromyalgia.


Using deep learning to examine street view green and blue spaces and their associations with geriatric depression in Beijing, China.
Residential green and blue spaces may be therapeutic for the mental health. However, solid evidence on the linkage between exposure to green and blue spaces and mental health among the elderly in non-Western countries is scarce and limited to exposure metrics based on remote sensing images (i.e., land cover and vegetation indices). Such overhead-view measures may fail to capture how people perceive the environment on the site. This study aimed to compare streetscape metrics derived from street view images with satellite-derived ones for the assessment of green and blue space; and to examine associations between exposure to green and blue spaces as well as geriatric depression in Beijing, China. Questionnaire data on 1190 participants aged 60 or above were analyzed cross-sectionally. Depressive symptoms were assessed through the shortened Geriatric Depression Scale (GDS-15). Streetscape green and blue spaces were extracted from Tencent Street View data by a fully convolutional neural network. Indicators derived from street view images were compared with a satellite-based normalized difference vegetation index (NDVI), a normalized difference water index (NDWI), and those derived from GlobeLand30 land cover data on a neighborhood level. Multilevel regressions with neighborhood-level random effects were fitted to assess correlations between GDS-15 scores and these green and blue spaces exposure metrics. The average cumulative GDS-15 score was 3.4 (i.e., no depressive symptoms). Metrics of green and blue space derived from street view images were not correlated with satellite-based ones. While NDVI was highly correlated with GlobeLand30 green space, NDWI was moderately correlated with GlobeLand30 blue space. Multilevel regressions showed that both street view green and blue spaces were inversely associated with GDS-15 scores and achieved the highest model goodness-of-fit. No significant associations were found with NDVI, NDWI, and GlobeLand30 green and blue space. Our results passed robustness tests. Our findings provide support that street view green and blue spaces are protective against depression for the elderly in China, yet longitudinal confirmation to infer causality is necessary. Street view and satellite-derived green and blue space measures represent different aspects of natural environments. Both street view data and deep learning are valuable tools for automated environmental exposure assessments for health-related studies.


Effect of Achilles tendon loading on plantar fascia tension in the standing foot.
The plantar fascia, which is one of the major arch-supporting structures of the human foot, sustains high tensions during weight-bearing. A positive correlation between Achilles tendon loading and plantar fascia tension has been reported. Excessive stretching and tightness of the Achilles tendon are thought to be the risk factors of plantar fasciitis but their biomechanical effects on the plantar fascia have not been fully addressed. A three-dimensional finite element model of the human foot and ankle, incorporating geometrical and material nonlinearity, was employed to investigate the loading response of the plantar fascia in the standing foot with different magnitudes of Achilles tendon loading. With the total ground reaction forces of one foot maintained at 350 N to represent half body weight, an increase in Achilles tendon load from (0-700 N) resulted in a general increase in total force and peak plantar pressure at the forefoot of up to about 250%. There was a lateral and anterior shift of the centre of pressure and a reduction in the arch height with an increasing Achilles tendon load as a result of the plantar flexion moment on the calcaneus. From the finite element predictions of simulated balanced standing, Achilles tendon forces of 75% of the total weight on the foot (350 N) were found to provide the closest match of the measured centre of pressure of the subject during balanced standing. Both the weight on the foot and Achilles tendon loading resulted in an increase in tension of the plantar fascia with the latter showing a two-times larger straining effect. Increasing tension on the Achilles tendon is coupled with an increasing strain on the plantar fascia. Overstretching of the Achilles tendon resulting from intense muscle contraction and passive stretching of tight Achilles tendon are plausible mechanical factors for overstraining of the plantar fascia.


Complete genome sequence of Arthrobacter sp. strain FB24.
Arthrobacter sp. strain FB24 is a species in the genus Arthrobacter Conn and Dimmick 1947, in the family Micrococcaceae and class Actinobacteria. A number of Arthrobacter genome sequences have been completed because of their important role in soil, especially bioremediation. This isolate is of special interest because it is tolerant to multiple metals and it is extremely resistant to elevated concentrations of chromate. The genome consists of a 4,698,945 bp circular chromosome and three plasmids (96,488, 115,507, and 159,536 bp, a total of 5,070,478 bp), coding 4,536 proteins of which 1,257 are without known function. This genome was sequenced as part of the DOE Joint Genome Institute Program.


Age-related dysfunction of the lacrimal gland and oxidative stress: evidence from the Cu,Zn-superoxide dismutase-1 (Sod1) knockout mice.
An imbalance between free radical generation and radical scavenging antioxidant systems results in oxidative stress, which has been associated with cell injury observed in many age-related diseases. The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase-1 (Sod1) in mice leads to many different phenotypes that resemble accelerated aging. In this study we examined the morphologic features and the secretory functions of the lacrimal glands in Sod1(-/-) mice. Lacrimal glands showed atrophy of acinar units; fibrosis; infiltration with CD4(+) T cells, monocytes, and neutrophils; increased staining with both 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine; increases in apoptotic cells; and the presence of the epithelial-mesenchymal transition in senescent Sod1(-/-) mice. Electron microscopy findings revealed evidence of epithelial-mesenchymal transition, presence of swollen and degenerated mitochondria, and the presence of apoptotic cell death in the lacrimal glands of senescent Sod1(-/-) mice. These alterations were also associated with the accumulation of secretory vesicles in acinar epithelial cells, decreased production of both stimulated and nonstimulated tears, and a decline in total protein secretion from the lacrimal glands. Our results suggest that Sod1(-/-) mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated lacrimal gland alterations.


Preliminary survey of ticks (Acari: Ixodidae) on cattle in northern Sudan.
In a cross sectional survey conducted during the period June 2001 to July 2002, the geographical distribution of ticks on cattle in the Sudan was determined. Seventeen locations were surveyed from Northern, Central, Eastern, Western, Blue Nile and White Nile Provinces. Total body collections of ticks were made from 20 cattle at each location. Four tick genera and 11 species were identified. The tick species collected included Amblyomma lepidum, Amblyomma variegatum, Boophilus decoloratus, Hyalomma anatolicum anatolicum, Hyalomma dromedarii, Hyalomma impeltatum, Hyalomma marginatum rufipes, Hyalomma truncatum, Rhipicephalus evertsi evertsi, Rhipicephalus sanguineus group and Rhipicephalus simus simus. Major ecological changes have occurred due to extensive animal movement, deforestation, desertification and establishment of large mechanized agricultural schemes. These factors have certainly affected the distribution of ticks and tick-borne diseases in the Sudan. The absence of A. variegatum and A. lepidum in northern Sudan was not surprising, since these tick species are known to survive in humid areas and not in the desert and semi-desert areas of northern Sudan. The absence of B. annulatus in northern and central Sudan is in accordance with the finding that this tick species is restricted to the southern parts of the central Sudan. The presence of H. anatolicum anatolicum in Um Benin in relatively high abundance is an interesting finding. The present finding may indicate that the southern limit of this species has changed and moved southwards to latitude 13 degrees N. It is concluded that major changes in tick distribution have taken place in the Sudan.


A randomized, double-blind, placebo-controlled trial of oral montelukast in acute asthma exacerbation.
Leukotriene receptor antagonists (LTRAs) are well established in the management of outpatient asthma. However, there is very little information as to their role in acute asthma exacerbations. We hypothesized that LTRAs may accelerate lung function recovery when given in an acute exacerbation. A randomized, double blind, placebo-controlled trial was conducted at the Aga Khan University Hospital to assess the efficacy of oral montelukast on patients of 16 years of age and above who were hospitalized with acute asthma exacerbation. The patients were given either montelukast or placebo along with standard therapy throughout the hospital stay for acute asthma. Improvements in lung function and duration of hospital stay were monitored. 100 patients were randomized; their mean age was 52 years (SD +/- 18.50). The majority were females (79%) and non-smokers (89%). The mean hospital stay was 3.70 ± 1.93 days with 80% of patients discharged in 3 days. There was no significant difference in clinical symptoms, PEF over the course of hospital stay (p = 0.20 at day 2 and p = 0.47 at day 3) and discharge (p = 0.15), FEV1 at discharge (p = 0.29) or length of hospital stay (p = 0.90) between the two groups. No serious adverse effects were noted during the course of the study. Our study suggests that there is no benefit of addition of oral montelukast over conventional treatment in the management of acute asthma attack. 375-Med/ERC-04.


Characterization of Fecal Microbiota with Clinical Specimen Using Long-Read and Short-Read Sequencing Platform.
Accurate and rapid identification of microbiotic communities using 16S ribosomal (r)RNA sequencing is a critical task for expanding medical and clinical applications. Next-generation sequencing (NGS) is widely considered a practical approach for direct application to communities without the need for in vitro culturing. In this report, a comparative evaluation of short-read (Illumina) and long-read (Oxford Nanopore Technologies (ONT)) platforms toward 16S rRNA sequencing with the same batch of total genomic DNA extracted from fecal samples is presented. Different 16S gene regions were amplified, bar-coded, and sequenced using the Illumina MiSeq and ONT MinION sequencers and corresponding kits. Mapping of the sequenced amplicon using MinION to the entire 16S rRNA gene was analyzed with the cloud-based EPI2ME algorithm. V3-V4 reads generated using MiSeq were aligned by applying the CLC genomics workbench. More than 90% of sequenced reads generated using distinct sequencers were accurately classified at the genus or species level. The misclassification of sequenced reads at the species level between the two approaches was less substantial as expected. Taken together, the comparative results demonstrate that MinION sequencing platform coupled with the corresponding algorithm could function as a practicable strategy in classifying bacterial community to the species level.


Higher HDL cholesterol is associated with better cognitive function: the Maine-Syracuse study.
Few studies have examined associations between different subcategories of cholesterol and cognitive function. We examined relationships between total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride levels and cognitive performance in the Maine-Syracuse Longitudinal Study, a community-based study of cardiovascular risk factors. Cross-sectional analyses were undertaken on data from 540 participants, aged 60 to 98 years, free of dementia and stroke. TC, HDL, LDL, and triglyceride levels were obtained. Cognitive function was assessed using a thorough neuropsychological test battery, including domains of cognitive function indexed by multiple cognitive tests. The cognitive outcomes studied were as follows: Visual-Spatial Memory and Organization, Verbal and Working Memory, Scanning and Tracking, Abstract Reasoning, a Global Composite score, and the Mini-Mental State Examination (MMSE). Significant positive associations were observed between HDL-cholesterol and the Global Composite score, Working Memory, and the MMSE after adjustment for demographic and cardiovascular risk factors. Participants with desirable levels of HDL (≥60 mg/dL) had the highest scores on all cognitive outcomes. There were no significant associations observed between TC, LDL, or triglyceride concentrations and cognition. In older individuals, HDL-cholesterol was related to a composite of Working Memory tests and for general measures of cognitive ability when adjusted for cardiovascular variables. We speculate that persons over 60 are survivors and thus less likely to show cognitive deficit in relation to TC, LDL-cholesterol, and triglycerides. Longitudinal studies are needed to examine relations between specific cognitive abilities and the different subcategories of cholesterol.


Mutant IDH1 Dysregulates the Differentiation of Mesenchymal Stem Cells in Association with Gene-Specific Histone Modifications to Cartilage- and Bone-Related Genes.
Somatic mutations in the isocitrate dehydrogenase (IDH)1/2 genes endow encoding proteins with neomorphic activity to produce the potential oncometabolite, 2-hydroxyglutarate (2-HG), which induces the hypermethylation of histones and DNA. The incidence of IDH1/2 mutations in cartilaginous tumors was previously shown to be the highest among various types of tumors, except for those in the central nervous system. Mutations have been detected in both benign (enchondromas) and malignant (chondrosarcomas) types of cartilaginous tumors, whereas they have rarely been found in other mesenchymal tumors such as osteosarcomas. To address this unique tumor specificity, we herein examined the effects of IDH1 R132C, which is the most prevalent mutant in cartilaginous tumors, on the differentiation properties of human mesenchymal stem cells (hMSCs). The induction of the IDH1 R132C gene into MSCs markedly increased the amount of 2-HG and up-regulated global histone methylation. The induction of IDH1 R132C promoted the chondrogenic differentiation of hMSCs by enhancing the expression of SOX9 and COL2A1 genes in association with an increase in the active mark (H3K4me3), but disrupted cartilage matrix formation. On the other hand, IDH1 R132C inhibited expression of the ALPL gene in association with an increase in the repressive mark (H3K9me3), and subsequently inhibited the osteogenic properties of hMSCs and human osteosarcoma cells. Since osteogenic properties are an indispensable feature for the diagnosis of osteosarcoma, the inhibitory effects of IDH1 R132C on osteogenic properties may contribute to the lack of osteosarcomas with the IDH1 R132C mutation. These results suggested that IDH1 R132C contributed to the formation of cartilaginous tumors by dysregulating the chondrogenic and osteogenic differentiation of hMSCs via gene-specific histone modulation.


Effects of Maturity and Determinacy in Soybean on Host-Parasite Relationships of Heterodera glycines.
The effects of soybean maturity and determinacy on the host-parasite relationships of Heterodera glycines were investigated in a field microplot study over 2 years. Determinate and indeterminate isolines of the maturity group (MG) III cultivar Williams 82 and the MG V cultivar Essex were grown in microplots artificially infested with a race 3 isolate of H. glycines at three initial population (Pi) densities (0, 300, and 3,000 eggs/100 cm(3) soil). Soybean seed yields, nematode final population (Pf) densities and reproductive index (Pf/Pi), and root colonization by Macrophomina phaseolina, the causal agent of charcoal rot, were monitored in each year. Seed yields were reduced (P </= 0.05) in the presence of H. glycines in both years, but losses were greater in 1996 in the absence of drought stress. Yield loss was lower (P </= 0.06) for the determinate isoline of Essex than for the other cultivar-isoline treatments across years. Nematode reproduction was density-dependent in the more conducive environment of 1996 but was unaffected by soybean maturity or determinacy traits. Root colonization by M. phaseolina increased (P </= 0.05) in the presence of high H. glycines densities on determinate, but not indeterminate, isolines. Differences in H. glycines-induced yield loss among cultivar-isoline treatments were not related to nematode reproduction, M. phaseolina colonization, or environmental stresses. These results indicate that the effects of soybean maturity and determinacy on H. glycines-soybean interactions are not independent and that their combined effects must be considered in geographic regions where both traits vary.


Optimizing the Detection of Preperimetric Glaucoma by Combining Structural and Functional Tests.
We evaluated the performance of low contrast achromatic (LLA) multifocal visual evoked potentials (mfVEP) in preperimetric glaucoma and compared its diagnostic performance to other early diagnostic tests. We identified the clinically most useful tests and combinations in preperimetric glaucoma. We studied 59 patients with at least one glaucomatous disc, with normal, reliable visual fields in that eye, and 17 normal controls. All participants underwent complete ophthalmic examination including Humphrey visual fields (HVF), short wavelength automated perimetry (SWAP), frequency doubling perimetry (FDT Matrix), Spectralis optical coherence tomography (OCT), Heidelberg retinal tomography (HRT 3), and color stereoscopic optic disc photographs. We recorded mfVEPs using LLA stimulation. We studied 85 eyes of 59 patients (64.89 ± 8.15 years) and 34 eyes of 17 controls (64.28 ± 13.06 years; P = 0.64). Heidelberg retinal tomography and LLA mfVEP demonstrated the best sensitivities (50.6% and 51.8%, respectively) in identifying preperimetric glaucoma, and were not significantly different from each other. Both tests had significantly better sensitivity than all other tests (P < 0.0001). Of the eyes, 76.5% were identified by the combination of (any one of) LLA mfVEP and HRT. Sensitivity of the combination was significantly better than any of the individual tests (P < 0.05 for all pairs), or any other combinations of tests, with better negative than positive predictive value. The LLA mfVEP test identified approximately 50.6% eyes with preperimetric glaucoma, which was significantly higher than other perimetric methods, and similar to HRT. The combination of LLA mfVEP and HRT had exceptionally high sensitivity of 76.5% for preperimetric glaucoma.


Clinical and roentgenographic scoring systems for assessing bronchopulmonary dysplasia.
Because investigation of bronchopulmonary dysplasia (BPD) has been hampered by imprecise methods for diagnosis and grading of severity, we evaluated new clinical and roentgenographic scoring systems in neonates with severe respiratory distress. The study population included 110 premature neonates who were admitted consecutively over a two-year period and who required mechanical ventilation. The clinical scoring system used measures of gas exchange, respiratory distress, and growth rate; roentgenographic scoring involved numerical assessment of features characteristic of BPD. A significant correlation was noted at 21 days of age between clinical and roentgenographic scores. In a linear stepwise multiple regression, we found that the best predictors of clinical score were birth weight (ie, degree of prematurity) and roentgenographic score. With further development and validation, BPD scoring should be helpful by improving our understanding of the epidemiology of this disease, providing a means for evaluation of treatment, and facilitating multicenter investigations.


Redefining hypotension in the elderly: normotension is not reassuring.
Recent debate concerns the most appropriate definition of hypotension. Some have advocated raising the systolic blood pressure (BP) threshold to 110 mm Hg while others favor 80 mm Hg. The optimal definition of hypotension differs by age group. An analysis was performed of trauma victims 18 years and older in the National Trauma Data Bank, excluding burn injury patients and those with incomplete data. Injured patients who were hospitalized in various trauma centers across the continental United States. Three age groups were identified for analysis as follows: 18 to 35 years, 36 to 64 years, and 65 years and older. One hundred one multiple logistic regression analyses were performed for each population. Hypotension was sequentially defined as an emergency department systolic BP (SBP) of 50 to 150 mm Hg to see which model best predicted mortality, adjusting for demographic and injury covariates. The discriminatory power of each model was measured using the area under the receiver operating characteristic (AUROC) curve. Optimally defined hypotension was identified as the model with the highest AUROC curve. In-hospital mortality. A total of 902,852 patients (median age, 44 years; 66.2% men) were analyzed. Overall mortality was 4.1%. Optimal emergency department SBP cutoff values for hypotension were 85 mm Hg for patients aged 18 to 35 years, 96 mm Hg for patients aged 36 to 64 years, and 117 mm Hg for elderly patients. For patients younger than 65 years, the classic definition of hypotension as an emergency department SBP less than 90 mm Hg remains optimal. With increasing involvement of elderly individuals in trauma and their peculiarity as a comorbid state, there is a need to redefine what is presently defined as a cutoff value for hypotension in elderly patients.


Dutasteride: a dual 5-alpha reductase inhibitor for the treatment of symptomatic benign prostatic hyperplasia.
To review the pharmacology, pharmacokinetics, efficacy, safety, drug interactions, and dosing recommendations of dutasteride, a 5-alpha reductase inhibitor for benign prostatic hyperplasia (BPH). A MEDLINE search (1966-February 2006) was conducted to extract human research data in the English language on dutasteride. Search terms included benign prostatic hyperplasia, dutasteride, and finasteride. The reference lists of articles identified through this search process, the manufacturer's Web site, and dutasteride prescribing information were also examined. All published studies and clinical data from the manufacturer were included, with emphasis placed on randomized, controlled trials. Dutasteride is approved for the treatment of symptomatic BPH in men with an enlarged prostate to improve urinary symptoms, reduce the risk of acute urinary retention, and reduce the need for BPH-related surgical interventions. Compared with placebo, dutasteride has been shown to significantly improve BPH symptoms, reduce the incidence of acute urinary retention and BPH-related surgery, and improve BPH-related quality of life. Few published data exist comparing dutasteride with finasteride. The most common adverse effects of dutasteride include ear, nose, and throat infection; malaise; headache; dizziness; and musculoskeletal pain. Clinical trials, sponsored primarily by the manufacturer, have shown dutasteride to be an effective treatment of BPH compared with placebo and to likely possess efficacy similar to that of finasteride. Further studies are needed to gain a more clear understanding of any clinically significant differences between dutasteride and finasteride.


Dibenzo[1,2,5]thiadiazepines are non-competitive GABAA receptor antagonists.
A new process for obtaining dibenzo[c,f][1,2,5]thiadiazepines (DBTDs) and their effects on GABA(A) receptors of guinea pig myenteric neurons are described. Synthesis of DBTD derivatives began with two commercial aromatic compounds. An azide group was obtained after two sequential reactions, and the central ring was closed via a nitrene to obtain the tricyclic sulfonamides (DBTDs). Whole-cell recordings showed that DBTDs application did not affect the holding current but inhibited the currents induced by GABA (I(GABA)), which are mediated by GABA(A) receptors. These DBTDs effects reached their maximum 3 min after application and were: (i) reversible, (ii) concentration-dependent (with a rank order of potency of 2c = 2d > 2b), (iii) mediated by a non-competitive antagonism, and (iv) only observed when applied extracellularly. Picrotoxin (which binds in the channel mouth) and DBTDs effects were not modified when both substances were simultaneous applied. Our results indicate that DBTD acted on the extracellular domain of GABA(A) channels but independent of the picrotoxin, benzodiazepine, and GABA binding sites. DBTDs used here could be the initial model for synthesizing new GABA(A) receptor inhibitors with a potential to be used as antidotes for positive modulators of these receptors or to induce experimental epilepsy.


On the temporal behavior of Nd3+ random lasers.
The temporal dynamics of random laser emission from Nd-doped crystal powders has been investigated by using an improved detection device. The precise conditions to detect high contrast, fast oscillations are described. The measured period is about one order of magnitude shorter than the one given in the literature for relaxation oscillations in these materials. The origin of these differences is discussed.


Chemical-garden formation, morphology, and composition. I. Effect of the nature of the cations.
We have grown chemical gardens in different sodium silicate solutions from several metal-ion salts--calcium chloride, manganese chloride, cobalt chloride, and nickel sulfate--with cations from period 4 of the periodic table. We have studied their formation process using photography, examined the morphologies produced using scanning electron microscopy (SEM), and analyzed chemical compositions using X-ray powder diffraction (XRD) and energy dispersive X-ray analysis (EDX) to understand better the physical and chemical processes involved in the chemical-garden reaction. We have identified different growth regimes in these salts that are dependent on the concentration of silicate solution and the nature of the cations involved.


Prophylactic Efficacy of Quercetin 3-β-O-d-Glucoside against Ebola Virus Infection.
Ebola outbreaks occur on a frequent basis, with the 2014-2015 outbreak in West Africa being the largest one ever recorded. This outbreak has resulted in over 11,000 deaths in four African countries and has received international attention and intervention. Although there are currently no approved therapies or vaccines, many promising candidates are undergoing clinical trials, and several have had success in promoting recovery from Ebola. However, these prophylactics and therapeutics have been designed and tested only against the same species of Ebola virus as the one causing the current outbreak. Future outbreaks involving other species would require reformulation and possibly redevelopment. Therefore, a broad-spectrum alternative is highly desirable. We have found that a flavonoid derivative called quercetin 3-β-O-d-glucoside (Q3G) has the ability to protect mice from Ebola even when given as little as 30 min prior to infection. Furthermore, we have demonstrated that this compound targets the early steps of viral entry. Most promisingly, antiviral activity against two distinct species of Ebola virus was seen. This study serves as a proof of principle that Q3G has potential as a prophylactic against Ebola virus infection.


Prolonged water immersion. Effects on blood pressure maturation in normotensive rats.
The purpose of this experiment was to study the impact of simulated microgravity and of chronic removal of hydrostatic pressure gradients on blood pressure maturation and body growth in rats. A special device was developed in our laboratory to transfer prolonged "dry" water immersion (a technique that has been used for training astronauts under hypogravic conditions) to six Sprague-Dawley test rats (immersion-G group). The time course of heart rate, systolic blood pressure, urinary output, and body weight was monitored from weaning to maturity and then compared with those responses from six sex- and age-matched Sprague-Dawley rats grown in a gravity environment (group G). A downward shift in systolic blood pressure and body weight maturation curves was observed in immersion-G rats from the age of 60 days. Cessation of dry water immersion produced a gradual, significant rise in systolic blood pressure but not in body weight to control values. No marked changes in heart rate and urinary output between G and immersion-G rats were noticed throughout the investigation. Our results provide indirect evidence that an interference in the natural history of blood pressure maturation was introduced by immersion, which dissociated the effects of body weight increase during growth from the effects of ageing per se. It is concluded that the physiological increase in systolic blood pressure during growth is partly gravity-dependent.


Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients: a cross-sectional study from the Big Data Sjögren Project Consortium.
To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis. The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed. We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69). This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.


The serpin secreted by Brugia malayi microfilariae, Bm-SPN-2, elicits strong, but short-lived, immune responses in mice and humans.
Understanding the basic immunology of an infectious disease requires insight into the pattern of T cell reactivity and specificity. Although lymphatic filariasis is a major tropical disease, the predominant T cell Ags of filarial species such as Brugia malayi are still undefined. We have now identified a prominent T cell Ag from B. malayi microfilariae (Mf) as Bm-SPN-2, a serpin secreted exclusively by this stage. Mf-infected mice mounted strong, but short-lived, Bm-SPN-2-specific Th1 responses, measured by in vitro production of IFN-gamma, but not IL-4 or IL-5, 14 days postinfection. By day 35, responsiveness to Bm-SPN-2 was lost despite enhanced reactivity to whole Mf extract. Single immunization with Mf extract also stimulated typical Th1 reactions to Bm-SPN-2, but IgG1 Ab responses dominated after repeated immunizations. Human patients displayed potent humoral responses to Bm-SPN-2 in both IgG1 and IgG4 subclasses. Thus, 100% (20 of 20) of the microfilaremic (MF(+)) patients bore IgG4 responses to Bm-SPN-2, while only 30% of endemic normal subjects were similarly positive. Following chemotherapy, Bm-SPN-2-specific Abs disappeared in 12 of 13 MF(+) patients, although the majority remained seropositive for whole parasite extract. PBMC from most, but not all, endemic subjects were induced to secrete IFN-gamma when stimulated with Bm-SPN-2. These findings demonstrate that Bm-SPN-2 is recognized by both murine and human T and B cells and indicate that their responses are under relatively stringent temporal control. This study also provides the first example of a stage-specific secreted molecule that acts as a major T cell Ag from filarial parasites and is a prime candidate for a serodiagnostic probe.


Assessment of tobacco dependence curricula in U.S. dental hygiene programs.
Tobacco dependence education (TDE) continues to be a vital component of dental hygiene curricula-made even more important by the fact that tobacco cessation in adults in the United States has stagnated over the past ten years. This study was undertaken to assess the salient characteristics of TDE in U.S. dental hygiene programs. A fifty-one question survey was mailed to the program directors of all 283 accredited dental hygiene programs during the 2007-08 school year (this number does not include the programs in Illinois, which were excluded since they had participated in a previous study). A total of 187 schools returned the survey for a return rate of 66 percent. Curricular content, minutes spent on each topic, existing level of clinical competence measured, expected level of clinical competence, and resources used were assessed. Respondents reported an average of 6.7 hours spent on all identified components of tobacco education. While 77 percent of respondents reported formally assessing whether a student asked if a patient used tobacco, only 26 percent indicated having a formal competency utilizing all of the U.S. Public Health Service's Clinical Practice Guideline 5 As and 5 Rs. In contrast, 72 percent of program directors reported expecting their graduates to be competent in a moderate intervention that included all 5 As. Though there is a clear commitment to TDE among dental hygiene programs in the United States, we recommend training to a more intensive level of TDE in order to facilitate broader adoption of comprehensive, evidence-based guidelines.


Streptococcus mutans serotype c tagatose 6-phosphate pathway gene cluster.
DNA cloned into Escherichia coli K-12 from a serotype c strain of Streptococcus mutans encodes three enzyme activities for galactose utilization via the tagatose 6-phosphate pathway: galactose 6-phosphate isomerase, tagatose 6-phosphate kinase, and tagatose-1,6-bisphosphate aldolase. The genes coding for the tagatose 6-phosphate pathway were located on a 3.28-kb HindIII DNA fragment. Analysis of the tagatose proteins expressed by recombinant plasmids in minicells was used to determine the sizes of the various gene products. Mutagenesis of these plasmids with transposon Tn5 was used to determine the order of the tagatose genes. Tagatose 6-phosphate isomerase appears to be composed of 14- and 19-kDa subunits. The sizes of the kinase and aldolase were found to be 34 and 36 kDa, respectively. These values correspond to those reported previously for the tagatose pathway enzymes in Staphylococcus aureus and Lactococcus lactis.


Impact of Phytolacca americana extracts on gene expression of colon cancer cells.
Native Americans have used Phytolacca americana to treat breast ailments, gastrointestinal disorders, rashes, and inflammation. Some anti-cancer and anti-viral research has been reported on this perennial herb, but none has been published concerning the effects of its extracts on cancer cell genes. In this study, changes in gene expression at the transcription level were evaluated in HCT-116 colon cancer cells after exposure to P. americana ethanol extract and its water fraction using the Human Cancer Pathway Finder PCR Array. Of the genes significantly affected in HCT-116 cells exposed to the ethanol extract at 3200 µg/ml, changes in expression of MYC, PLAU, and TEK may benefit the treatment of colon cancer. Exposing the cells to 1600 µg/ml of the water fraction resulted in several gene changes that may also be beneficial in the treatment of colon cancer: NME4, TEK, and THBS1. A few genes on this array that are known to play a specific role in colon cancer had activities changed in a way that may be detrimental in the treatment of colon cancer. Further studies should be performed to understand how these changes would impact colon cancer treatment.